Chronic renal insufficiency is associated with a complex suppression of immune response. More than one-sixth of patients maintained by chronic hemodialysis die of infection. Uremic serum often has immunosuppressive properties. Immunosuppressive factor in the serum of uremic rats and in sera of some uremic patients is a very low density lipoprotein. Since uremia is frequently complicated by hypertriglyceridemia, the mechanisms of immunosuppression and hyperlipidemia in some patients may be related. The discrete fraction of immunosuppressive very low density lipoprotein isolated from the serum of uremic rats will be biochemically characterized and its metabolic origin will be studied. Sera of other uremic patients contain dialyzable immunosuppressive factor(s) purportedly belonging to uremic "middle molecules". The "middle molecules" fraction of human uremic serum will be isolated and its role in immunosuppressive effects will be evaluated. The in vitro immune potential of peripheral white blood cells of uremic patients will be analyzed and effects of their sera on various cellular functions in vitro will be evaluated. Nephrotic syndrome is also associated with increased sensitivity to infection which may be caused by changes in immune potential. We will use the experience gained in analysis of immune response in uremia for comprehensive study of cellular immune potential and immunosuppressive properties of sera in patients with nephrotic syndrome. The observed changes in immune potential will be studied in context of the etiology, duration and management of the disease. A better understanding of the mechanism of pathological suppression of immune responses ought to provide a rational basis for the improved treatment and management of these patients.